Losartan, an antagonist of AT1 receptor for angiotensin II, attenuates lipopolysaccharide-induced acute lung injury in rat.
Angiotensin II (Ang II) plays an important role in inflammatory process. Acute lung injury (ALI), an inflammatory disorder of the lung, is commonly associated with endotoxemia; however, the mechanism that endotoxin (lipopolysaccharide, LPS) induces the inflammatory response in ALI is not well defined. Here, we showed, in LPS-induced ALI rat model, that Ang II and Ang II type 1 (AT(1)) receptor were significantly increased in lung tissues, compared with those in controls. Meanwhile, nuclear factor (NF)-kappaB-DNA-binding activity, tumor necrosis factor (TNF)-alpha mRNA, and pneumocytic apoptosis were significantly increased. Moreover, pretreatment of rats with losartan, an antagonist of AT(1) receptor for Ang II, improved the inflammation, reduced the elevation of Ang II and AT(1) receptor, and inhibited NF-kappaB-DNA-binding activity, expression of TNF-alpha mRNA, and pneumocytic apoptosis. The data indicate that Ang II may mediate the inflammatory process in LPS-induced ALI through AT(1) receptor, which can be blocked by losartan.
Liu
Ling
L
Department of Critical Care Medicine, Nanjing Zhong-Da Hospital, Southeast University School of Medicine, Nanjing, China.
Qiu
Hai-Bo
HB
Yang
Yi
Y
Wang
Lian
L
Ding
Hui-Min
HM
Li
Hong-Peng
HP
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D019808:Losartan